Research on the relationship between resistin levels, metabolic health, and obesity has produced inconsistent findings across different ethnic groups, making it unclear whether lower resistin levels are associated with these conditions in Mexican-Americans. This cross-sectional study investigated the relationship between resistin, metabolic health, and obesity in an adult Mexican-American cohort (n = 1511) using multivariable linear regression analysis. Related adipokines (leptin and adiponectin) were measured simultaneously. Participants were categorized into four groups by metabolic health (healthy/unhealthy) and obesity (obese/non-obese) status. “Metabolically unhealthy” was defined as ≥2 cardiometabolic abnormalities. Obesity was defined as a BMI ≥ 30 kg/m². We also investigated the associations of related proinflammatory cytokines, demographic/anthropometric variables, and medications with each outcome variable of interest. The results showed no statistically significant differences in resistin levels between the groups. Leptin was higher and adiponectin was lower in groups with obesity and/or metabolically unhealthy status. The resistin findings contrast studies in other populations, while other leptin and adiponectin findings confirm those seen in many ethnic groups. Thiazolidinedione use was associated with lower resistin, confirming earlier research. These findings suggest that resistin’s role in metabolic health may be different in Mexican-Americans compared to other populations.